99055-42-2Relevant academic research and scientific papers
2-Aminothiazole Derivatives as Selective Allosteric Modulators of the Protein Kinase CK2. 2. Structure-Based Optimization and Investigation of Effects Specific to the Allosteric Mode of Action
Bestgen, Beno?t,Kufareva, Irina,Seetoh, Weiguang,Abell, Chris,Hartmann, Rolf W.,Abagyan, Ruben,Le Borgne, Marc,Filhol, Odile,Cochet, Claude,Lomberget, Thierry,Engel, Matthias
, p. 1817 - 1836 (2019/02/26)
Protein CK2 has gained much interest as an anticancer drug target in the past decade. We had previously described the identification of a new allosteric site on the catalytic α-subunit, along with first small molecule ligands based on the 4-(4-phenylthiazol-2-ylamino)benzoic acid scaffold. In the present work, structure optimizations guided by a binding model led to the identification of the lead compound 2-hydroxy-4-((4-(naphthalen-2-yl)thiazol-2-yl)amino)benzoic acid (27), showing a submicromolar potency against purified CK2α (IC50 = 0.6 μM). Furthermore, 27 induced apoptosis and cell death in 786-O renal cell carcinoma cells (EC50 = 5 μM) and inhibited STAT3 activation even more potently than the ATP-competitive drug candidate CX-4945 (EC50 of 1.6 μM vs 5.3 μM). Notably, the potencies of our allosteric ligands to inhibit CK2 varied depending on the individual substrate. Altogether, the novel allosteric pocket was proved a druggable site, offering an excellent perspective to develop efficient and selective allosteric CK2 inhibitors.
Inhibitors of calcium-activated chloride channels
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, (2017/11/07)
Provided herein are methods for identifying compounds that are inhibitors of a calcium-activated chloride channel. Aminothiophene and aminothiazole compounds, and compositions comprising these compounds, described herein that inhibit efflux of chloride th
Synthesis and antimicrobial evaluation of some novel 2-aminothiazole derivatives of 4-hydroxy-chromene-2-one
Vukovic, Nenad,Sukdolak, Slobodan,Solujic, Slavica,Milosevic, Tanja
experimental part, p. 491 - 496 (2009/04/04)
Syntheses of 2-aminothiazole derivatives of 4-hydroxy-chromene-2-one 2c-10c are reported in this paper. These compounds 2c-10c were prepared from 3-(2-bromoacetyl)-4-hydroxy-chromene-2-one 1 and corresponding thiourea derivatives 2b-10b using Hantzsch reaction. The structures of all compounds were confirmed by IR and 1H-NMR spectroscopy and elemental analyses. The molecules 2c-10c were evaluated for in vitro antimicrobial activity against ten bacteria and twelve fungi. All tested compounds exhibited antibacterial and antifungal activity.
Small-molecule screen identifies inhibitors of a human intestinal calcium-activated chloride channel
De La Fuente, Ricardo,Namkung, Wan,Mills, Aaron,Verkman, Alan S.
, p. 758 - 768 (2008/09/20)
Calcium-activated chloride channels (CaCCs) are widely expressed in mammalian tissues, including intestinal epithelia, where they facilitate fluid secretion. Potent, selective CaCC inhibitors have not been available. We established a high-throughput scree
